Long-running studies of Vietnam veterans have shed some light on how people respond to traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) and revealed some of the links between the two conditions, according to three high-profile researchers. But much of the underlying biology remains unknown—especially for blast-related injuries not often seen in Vietnam—limiting treatment options for those injured in the current wars, said the researchers, speaking during a panel on Sept. 24 at the Dana Center in Washington, D.C.

Their research has taken on increased urgency because of the large numbers of troops returning from Iraq with these conditions. Estimates suggest hundreds of thousands of Iraq and Afghanistan veterans have suffered at least mild TBI and up to 20 percent have PTSD symptoms, often simultaneously.

TBI is physical injury to the brain, either via a blow to the head or a penetrating object, showing a variety of physical and neurological symptoms. PTSD is a persistent state of anxiety that occurs after psychological trauma—essentially, “an illness of too-strong memory,” said Steven Hyman, provost of Harvard University. Symptoms include flashbacks, insomnia and difficulty coping with home and work life.

One hot area of research is the role of personality and training in stemming effects of TBI and PTSD. Studies of Vietnam prisoners of war show that some people are seemingly “invulnerable” to PTSD because of an “extreme psychological resilience,” said Dennis Charney, dean of the Mount Sinai School of Medicine. By employing elaborate coping mechanisms, such as writing novels in their head or visualizing building a house brick by brick, these prisoners were able to avoid PTSD symptoms or recover more speedily after their confinement, Charney said.

In TBI, intelligence is a key factor, said Jordan Grafman, a senior investigator at the National Institute for Neurological Disorders and Stroke. Vietnam veterans who scored higher on pre-injury intelligence tests or who had more schooling tend to recover from TBI faster than those who scored lower or had less, his research suggests. Studies continue to follow these veterans, now in their 50s and 60s, to assess TBI’s long-term effects, including whether it increases the risk of Alzheimer’s disease.

But the findings might not be of immediate help to the current crop of injured veterans, Grafman added, because many of them are suffering different injuries than those common in Vietnam. In particular, soldiers now are surviving blasts by improvised explosive devices thanks to better body armor, and doctors are seeing fewer direct shrapnel injuries to the brain. But many soldiers appear to have brain injuries solely from the blasts’ shockwaves, a poorly understood phenomenon.

One connection between PTSD and TBI may lie in an imbalance in the brain’s fear response, Hyman said. The amygdala helps vivid memories form during intense emotional experiences—“who doesn’t remember where they were on 9/11?” he said—but that fear response can be modulated by the prefrontal cortex. Also, soldiers with damage to their amygdalas have lower rates of PTSD, he said.

Personality and experience play a role here, too, Hyman said. People with training against stressful situations or who have led more-adventurous lives overall tend to get PTSD less often. “These experiences are really important to how you deal with trauma,” he said. People who are optimistic, especially if tempered by “realistic appraisals” of the situation, also appear to suffer less-lingering trauma.

The findings suggest that psychological training might be a good preventive treatment, Hyman said. Another option might be drugs that prevent the formation or blunt the impact of memories, he said, though this kind of treatment would raise a number of ethical questions. A recent research paper in Nature Neuroscience suggested one potential target: beta-catenin, a protein “hub” associated with memories of fearful events.

Research into the exact physical causes and possible treatments for PTSD and TBI will continue for decades to come, all three speakers said. One area currently under investigation, Grafman said, is diffusion tensor imaging, a form of MRI that looks at water diffusion. This would allow us “to measure the integrity of connections in brain injury,” he said, which is important because many researchers believe both disorders may cause disruptions in the networking of white matter in the brain that are largely invisible to other scanning techniques.